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BACKGROUND: Recent evidence suggests that the type I 3β-hydroxysteroid dehydrogenase, a steroidogenic enzyme encoded by the HSD3B1 gene, could be involved in aldosterone production and that genetic variation in HSD3B1 is associated with blood pressure. These findings challenge the long-standing hypothesis that all adrenocortical steroidogenesis is executed by the type II iso-enzyme, encoded by HSD3B2. METHODS: To verify these findings, the adrenal presence of HSD3B1 and its effect on aldosterone synthesis and blood pressure were studied in expression and genetic association analyses, respectively. Expression of HSD3B1 and HSD3B2 was investigated in various adrenocortical tissues (n = 15) and in primary adrenal cell cultures (n = 5) after stimulation with adrenocorticotropin and angiotensin II. Six tagging single nucleotide polymorphisms within the HSD3B1 gene were studied for association with blood pressure and hypertension in a meta-analysis of 4 Dutch cohorts (n = 11,192). RESULTS: HSD3B1 expression was minimal or absent in adrenocortical tissues, including 6 aldosterone-producing adenomas. In contrast with the ubiquitously expressed HSD3B2 mRNA, HSD3B1 levels were not stimulated by adrenocorticotropin or angiotensin II. No variants in the HSD3B1 gene were associated with blood pressure or the occurrence of hypertension. CONCLUSIONS: We found no evidence to support confirmation that HSD3B1 is involved in aldosterone synthesis in the human adrenal cortex or that genetic variation in HSD3B1 affects blood pressure or hypertension, favoring the hypothesis that all adrenocortical steroidogenesis is primarily dependent on the type II 3β-hydroxysteroid dehydrogenase.

Original publication

DOI

10.1093/ajh/hpu103

Type

Journal article

Journal

American journal of hypertension

Publication Date

01/2015

Volume

28

Pages

113 - 120

Addresses

Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Keywords

Adrenal Cortex, Cells, Cultured, Humans, Hypertension, Genetic Predisposition to Disease, Aldosterone, Multienzyme Complexes, Steroid Isomerases, Progesterone Reductase, RNA, Messenger, Risk Factors, Gene Expression Regulation, Enzymologic, Blood Pressure, Phenotype, Polymorphism, Single Nucleotide, Aged, Middle Aged, Netherlands, Female, Male, Genetic Association Studies